简介：Leptinistheproteinproductencodedbytheobese(ob)gene.Itisacirculatinghormoneproducedprimarilybytheadiposetissue.ob/obmicewithmutationsofthegeneencodingleptinbecomemorbidlyobese,infertile,hyperphagic,hypothermic,anddiabetic.Sincethecloningofleptinin1994,ourknowledgeinbodyweightregulationandtheroleplayedbyleptinhasincreasedsubstantially.Wenowknowthatleptinsignalsthroughitsreceptor,OB-R,whichisamemberofthecytokinereceptorsuperfamily.Leptinservesasanadipositysignaltoinformthebraintheadiposetissuemassinanegativefeedbackloopregulatingfoodintakeandenergyexpenditure.Leptinalsoplaysimportantrolesinangiogenesis,immunefunction,fertility,andboneformation.Humanswithmutationsinthegeneencodingleptinarealsomorbidlyobeseandrespondtoleptintreatment,demonstratingthatenhancingorinhibitingleptin'sactivitiesinvivomayhavepotentialtherapeuticbenefits.

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简介：In2001and2002,publicationoftheresultsofthreelargerandomizedcontrolledtriais(RCTs)changedourunderstandingoftherisksandbenefitsofhormonereplacementtherapy(HRT),leadingtonewguidancefromnationaladvisorybodiesonitsuse.Manyclinicaliyrelevantquestionsremainunanswered,butparadoxicallythereultsofrecenttrialsmayhavemadeitmoredifficulttodesignthestudiesnecessarytoanswerthesequestions.TheUKWISDOMtrial(oestrogen-progestogenvsplaceboinhealthywomen),forexample,hasbeendiscontinued.

简介：Anuranmetamorphosisinvolvessystematictransformationsofindividualorgansinathyroidhormone(TH)-dependentmanner.Morphologicalandcellularstudieshaveshownthattheremovaloflarvalorgans/tissuessuchthetailandthetadpoleintestinalepitheliumisthroughprogrammedcelldeathorapop-tosis.RecentmolecularinvestigationssuggestthatTHregulatesmetamorphosisbyregulatingtargetgeneexpressionthroughthyroidhormonereceptors(TRs),whichareDNA-bindingtranscriptionfactors.Cloning

简介：ObjectivesToobservetherelationshipbetweenThyroidHormone(TH)levelandbloodlipidlevelinthehealthyelderlywiththerapyofsmalldoseofTH.MethodsAtotalof120healthyoldpersonswererandomlydividedintotwogroups:60oldpersonsastreatmentgroupandother60personsascontrolgroup.Eachpersoninthetreatmentgrouptookathyroidtablet10mgdailycontinuouslyforsixmonthswhilethecontrolgrouptookVitB130mgdailyinsteadofthyroidtablet.ThelevelofTH,M-TSH,FT3,FT4,TT4,rT3,TC,TG,LDL-C,HDL-C,ApoA1weremeasuredintwogroupsbeforeandafterreceivingTHorVit.B1treatment.ResultsInthetreatmentgroupthelevelofTHincreasedobviously.AndTC,TG,LDL-ClevelsdecreasedalsotosomeextentwhileHDL-C,ApoAllevelsincreasedslightlywhichwassignificantwhencomparedwiththecontrolgroupandpre-treatmentgroup.ConclusionsTousesmalldoseofTHassupplementtreatmentcanincreasetheTHlevelofhealthyoldpersonsanddecreasethei

简介：AIM:Tocomparethecornealparametersofchildrenwithcongenitalisolatedgrowthhormonedeficiencyandhealthysubjects.METHODS:Inthiscross-sectional,prospectivestudy,50caseswithgrowthhormone(GH)deficiencytreatedwithrecombinantGHand71healthychildrenunderwentacompleteophthalmicexamination.Thecornealhysteresis(CH),cornealresistancefactor(CRF),Goldmann-correlatedintraocularpressure(IOPg)andcorneal-compensatedintraocularpressure(IOPcc)weremeasuredwiththeOcularResponseAnalyzer(ORA).Centralcornealthickness(CCT)wasmeasuredbyaultrasonicpachymeter.RESULTS:Themeanagewas13.0±3.0yearsintheGHdeficiencygroupconsistingof21femalesand29malesand13.4±2.4yearsinthehealthychildrengroupconsistingof41femalesand30males.Therewasnostatisticallysignificantdifferencebetweenthegroupsforgenderorage(Chi-squaretest,P=0.09;independentttest,P=0.28,respectively).ThemeandurationofrecombinantGHtherapywas3.8±2.4yinthestudygroup.ThemeanCH,CRF,IOPgandIOPccvalueswere11.0±2.0,10.9±1.9,15.1±3.3,and15.1±3.2mmHgrespectivelyinthestudygroup.Thesamevalueswere10.7±1.7,10.5±1.7,15.2±3.3,and15.3±3.4mmHgrespectivelyinthecontrolgroup.ThemeanCCTvalueswere555.7±40.6,545.1±32.5μminthestudyandcontrolgroupsrespectively.TherewasnostatisticallysignificantdifferencebetweenthetwogroupsforCH,CRF,IOPg,IOPccmeasurementsorCCTvalues(independentt-test,P=0.315,0.286,0.145,0.747,0.13respectively).CONCLUSION:OurstudysuggeststhatGHdeficiencydoesnothaveaneffectonthecornealparametersandCCTvalues.ThisobservationcouldbebecauseofthedurationbetweenthebeginningofdiseaseandthediagnosisandbeginningofGHtherapy.

简介：AbstractFibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly.

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简介：Anuranmetamorphosisinvolvessystematictransformationsofindividualorgansinathyroidhormone(TH)-dependentmanner.Morphologicalandcellularstudieshaveshownthattheremovaloflarvalorgans/tissuessuchthetailandthetadpoleintestinalepitheliumisthroughprogrammedcelldeathorapoptosis.RecentmolecularinvestigationssuggestthatTHregulatesmetamorphosisbyregulatingtargetgeneexpressionthroughthyroidhormonereceptors(TRs),whichareDNA-bindingtranscriptionfactors.CloningandcharacterizationofTHresponsegenesshowthatdiversegroupsofearlyresponsegenesareinducedbyTH.TheproductsoftheseTHresponsegenesarebelievedtodirectlyorindirectlyaffecttheexpressionand/orfunctionsofcelldeathgenes,whichareconservedatbothsequenceandfunctionlevelsindifferentanimalspecies.Amajorchallengeforfutureresearchliesatdeterminingthesignalingpathwaysleadingtotheactivationofapoptoticprocessesandwhetherdifferentdeathgenesareinvolvedintheregulationofapoptosisindifferenttissues/organstoeffecttissue-specifictransformations.

简介：AIM:Toinvestigatewhetherthesimultaneoustreatmentwithhumangrowthhormone(hGH)abolishesthenegativeeffectsofeverolimusonanastomotichealing.METHODS:Forty-eightmaleSprague-Dawley-ratswererandomizedtothreegroupsof16animalseach(Ⅰ:vehicle;Ⅱ:everolimus3mg/kgpo;Ⅲ:everolimus3mg/kgpo+hGH2.5mg/kgsc).AnimalswerepretreatedwithhGHand/oreverolimusdailyforsevendays.Thenastandardanastomosiswascreatedinthedescendingcolonandtreatmentwascontinuedforanothersevendays.Theanastomosiswasresectedintotoandtheburstingpressurewasassessedasamechanicalparameterofintestinalhealing.Moreover,biochemical(Hydroxyproline,PCNA,MPO,MMP-2andMMP-9)andhistological(celldensity,angiogenesis,amountofgranulationtissue)parametersofintestinalhealingwereassessed.RESULTS:AnastomoticburstingpressurewassignificantlyreducedbyeverolimusandasimultaneoustreatmentwithhGHresultedinconsiderablyhighervalues(Ⅰ:134±19mmHg,Ⅱ:85±25mmHg,Ⅲ:114±25mmHg;P<0.05,ⅠvsⅡ;P=0.09,ⅠvsⅢandⅡvsⅢ)HydroxyprolineconcentrationwassignificantlyincreasedbyhGHcomparedtoeverolimusalone(Ⅰ:14.9±2.5μg/mg,Ⅱ:8.9±3.6μg/mg,Ⅲ:11.9±2.8μg/mg;P<0.05,?ⅠvsⅡ/ⅢandⅡvsⅢ).ThenumberofMPO-positivecellswasreducedsignificantlybyhGHcomparedtoeverolimusalone(Ⅰ:10±1n/mm~2,Ⅱ:15±3n/mm~2,Ⅲ:9±2n/mm~2;P<0.05,ⅠvsⅡandⅡvsⅢ),whilethenumberofPCNA-positivecellswereincreasedbyhGH(Ⅰ:28±3/mm~2,Ⅱ:12±3/mm~2,Ⅲ:26±12/mm~2;P<0.05,?Ⅰ?vsⅡandⅡvsⅢ).Correspondingtothesebiochemicalfindings,HEhistologyrevealedsignificantlyincreasedamountofgranulationtissueinhGH-treatedanimals.CONCLUSION:InhibitionofintestinalwoundhealingbyeverolimusispartiallyneutralizedbysimultaeoustreatmentwithhGH.BothinflammationaswellascollagendepositionisinfluencedbyhGH.

简介：Hormonereplacementtherapy(HRT)isinuseformorethanahalfofcentury,butthequestionofindicationsandidealcandidatesforHRTremainsunclear.Postmenopausalwomenareapopulationwiththeincreasingrisksforcardiovasculardiseaseswhicharethemaincauseofdeathinthisgroup.Declineinoestrogenconcentrations

简介：CHAARTED是在荷尔蒙敏感的前列腺癌症独自除了雄激素剥夺治疗(ADT)对ADT与docetaxel的使用看早化疗的带ECOG的阶段III试用。在与ADT收到了化疗的那些在全面幸存显示出显著改进的试用的积极结果革命化了变形阉割敏感的前列腺癌症的治疗。除了全面幸存，第二等的端点象阉割抵抗的时间那样，PSA反应为收到了早化疗的病人也是重要的。

简介：backgroundStudiesshowedthatarterialelasticitychangesappearearlierthananystructuralchanges,therefore,itsaccurateevaluationcouldbeappliedatearlystagetopreventdisease.Echo-tracking(E-tracking)techniquecantrackthewallmotiontrajectoryinreal-time,calculatethechangeinvasculardiameterautomatically,andassessmentofvascularstiffnessandflexibilitydirectly.Thisarticleaimstoassessthechangeofelasticityofcarotidarteryafterhormonetherapy(HT)usingEcho-trackingtechnology.MethodsEcho-trackingwasusedtoevaluatethecarotidelasticmoduli,suchasthepressure-strainelasticmodulus(Eρ),stiffnessparameter(β),arterialcompliance(AC),pulsewaveconductingvelocity(PWVβ)andaugmentationindex(AI)byAlokaα10colorDopplerultrasounddiagnosissystem.ResultsEρ,βandPWVβinHTgroupweresignificantlylowerthanthoseinthecontrolgroup(P<0.01),whileACwasobviouslyhigherthanthecontrolgroup(P<0.01).E2wasnegativelyrelatedtoβ,EρandPWVβ(r=-0.607,r=-0.573,r=-0.574,P<0.001),whilepositivelyrelatedtoAC(r=0.574,P<0.001);endothelial-dependentdilatation(EDD)wasnegativelyrelatedtoβ,EρandPWVβ(r=-0.521,r=-0.411,r=-0.456,P<0.001),whilepositivelyrelatedtoAC(r=0.443,P<0.001);ButIMTwaspositivelyrelatedtoβ,EρandPWVβ(r=0.553,r=0.444,r=0.529,P<0.001),whilenegativelyrelatedtoAC(r=-0.400,P<0.001).ConclusionsArterialstiffnessincreasesandcompliancedecreasesinmenopausalwomen.AsEDDdecreasesarterialelasticityrecedes,andHTcanimprovearterialelasticity.E-trackingtechnologycandiscovertheearlychangesinarterialstiffnesseffectivelyanditismoresensitiveinfindingoutthechangesofstiffnessinearlyatherosclerosisthanIMTofcarotidartery.

简介：BydeterminationofthechangeofendogenoushormoneZr,iPA,GA3,IAAandABAduringdifferentflowerbuddifferentiationstagesofPhyllostachyspraecox,whichisidentifiedthroughbothfieldobservationandlabanalysis,andwiththereferencetothepreviousresearchachievementsonbambooflowering,thefloweringmechanismassumptionofPhyto-HormoneRegulationandGeneActivationofPh.praecoxisinducedinthisarticle:Bambooflowerbuddifferentiationcanbedividedinto3stages,i.e.flowerbudinduction,flowerbudinitiationandflowerbuddevelopment;Bambooleavessenseandreceivefloweringsignalsfromenvironmentstochangeitshormonelevel,esp.ratiosofiPA/ABAandiPA/GA3;FloweringgeneisactivatedoncetheratiosofiPA/ABAandiPA/GA3reachaproperthreshold,anditproducesDNAandRNAcarryingfloweringcodeandtransportsthemtotoporsidebudsnearby,andthenproteinnecessaryforflowerbuddifferentiationcomesout,asaresultofwhichtheflowerbudinductionistriggedandstarted,followedbyflowerbudinitiationanddevelopment.Intheinductionstage,ratioofC/Nisnearlyconstant,butincreasesintheinitiationstage.ThereforeitclarifiesthattherisingofC/Nratiodoesnotbringaboutbamboofloweringinitially,anditisafollow-upreactionsofprocessinitiationofbambooflowering.Itprovesthatbamboorhizomeisdirectlyinvolvedintheflowerbuddifferentiation.Thisassumptioncanwellexplainmysteriousphenomenaofbambooflowering,andbyintegratingthecurrentseveralassumptions,answerthedifficultandperplexingquestionsregardingbamboofloweringwhichhavenotbeenansweredbythepresentassumptions.

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简介：Theenhancedcardiaccontractilityeffectofhumanrecombinantgrowthhormone(hr-GH)onthecongestiveheartfailure(CHF)wasstudiedonthepig.Tobuildapigmodelofcongestiveheartfailure,atemporaryartificialcardiacpacemakerwasimplantedinthepig'sbodyandpacedat220beatsto240beatsperminutefor1week.Afterthemodelofcongestiveheartfailurewassuccessfullysetup,thefrequencyofthepacemakerwaschangedto150beatsto180beatsperminutetomaintaintheCHFmodelstable.Pigsweredividedintothreegroups:Thehr-GHgroupinwhich0.5mg/kgperdayofhr-GHwasadministratedintramuscularlyfor15days,theinjectioncontrolgroupinwhichanequalamountofphysiologicalsalinewasinjectedintramuscularly,andanormalcontrolgroup.Theleftventriculardiastolicendpressurewas(10.60±2.41)mmHginthehr-GHgroup,but(19.00±3.81)mmHginthesalinecontrolgroup(P＜0.01);Cardiacoutputwas(1.86±0.13)L/mininthehr-GHgroup,but(1.56±0.18)L/mininthesalinecontrolgroup(P＜0.05);Peripheralmin)-1inthesalinecontrolgroup(P＜0.05);±dp/dtmaxwas(2900±316.23)and(2280±286.36)inthehr-HGgroupandthesalinecontrolgrouprespectively(P＜0.05).Theresultsshowthathr-GHenhancesmyocardialcontractilityofCHF,andtheCHFmodelbuiltbyatemporaryartificialcardiacpacemakeratahighrateofstimulationisreasonableandapplicable.

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简介：AbstractIncreasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

简介：AbstractObjective:This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM.Methods:We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18-40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10-14, 15-26, 23-31, and 33-39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk.Results:SHBG levels at gestational weeks 10-14 were significantly inversely associated with fasting insulin (r= -0.17, P= 0.01) and insulin resistance as measured by HOMA-IR (r= -0.17, P= 0.01) at gestational week 15-26. SHBG at gestational weeks 10-14 and 15-26 was lower in cases than controls (mean ± standard deviation: (204.0±97.6) vs. (220.9±102.5) nmol/L, P= 0.16 and (305.6±124.3) vs. (322.7±105.1) nmol/L, P= 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, P < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76-0.95, P= 0.01) for GDM.Conclusion:Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.